The aim of the research project proposed here is to localize and characterize leech monoclonal antibodies (mABs) using histological techniques. mABs have been generated against the leech nervous system and 40 of them recognize small subsets of neurons. In many cases, the subsets include functionally related neurons. Immunocytochemical visualization of mABs demonstrates mAB binding to neuronal cell bodies, axons and axonal endings. Pilot studies have shown that different mABs bind to different subcellular organelles, that mAB-stained fibers occupy sterotypical positions within the connective (the major axon pathway of the leech), that one mAB is associated with vessicles in a small population of axons, and that another recognizes a constituent of CNS muscle cell cytoplasm. The studies proposed here include: mapping the distribution of mAB-stained neurons at the light and electron microscopic levels; characterizing mABs subcellular staining patterns; and correlating mAB-stained neurons with neurons identified by other histological and physiological means. mABS give us the opportunity to study two issues in neurobiology. Principles of organization and circuitry can be approached through the delineation of subgroups from the entire neuronal population. mAB marking of specific subsets of neurons shows that there are chemical moieties common to related neurons, suggesting that neuronal specificity may be a result of intrinsic chemical factors. Leech mABs offer a new approach to neurobiological investigation which will increase our understanding of the organization and function of the nervous system.